A Multicenter, Double Blinded Randomized Controlled Trial of a Novel Oral Synbiotic Formula in Reducing Advanced Adenoma Recurrence and Colorectal Neoplasia-related Bacterial Gene Markers
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 649
- 试验地点
- 2
- 主要终点
- The incidence of metachronous recurrent advanced colorectal neoplasia at year 1 (local or at other sites).
研究概览
简要总结
This multicenter, double blinded randomized controlled trial aims to assess the efficacy of a novel oral synbiotic formula (SMT04) in reducing advanced adenoma recurrence and colorectal neoplasia-related bacterial gene markers after endoscopic resection of colorectal advanced neoplasia.
详细描述
Recent evidence has demonstrated the association between altered gut microbiome environment and the progression of colorectal cancer (CRC) from its precancerous lesions. Some pathogenic species of bacteria, including Fusobacterium nucleatum, Escherichia Coli and Bacteroides fragilis, have shown to be significantly enriched in CRC patients. This gut dysbiosis process also brings with its diagnostic potential for recurrent adenomas. Previous study found a panel of bacterial gene markers, including "m3" from Lachnoclostridium, F. nucleatum (Fn), Bacteroides clarus (Bc) and Clostridium hathewayi (Ch) could be used in detecting adenoma recurrence after polypectomy in a retrospective study. In addition, these microbial biomarkers may have prognostic potential and provide an option as therapeutic target.
Probiotics, including the genera Bifidobacterium and Lactobacillus, have shown to be able to inhibit tumorigenesis and progression of CRC in animal studies. Prebiotics are non-digestible dietary ingredients with protective effects against cancer by selectively stimulating the growth and activity of beneficial colonic microbiota. The combination of probiotics and prebiotics, known as synbiotic, may be more efficient in preventing CRC than either one alone.
The investigators' unpublished data showed that the new probiotic formula containing Bifidobacterium strains has a negative correlation with CRC-related bacterial gene markers. Subjects treated with SMT04 showed significantly higher levels of the individual Bifidobacterium species at week 2 to week 5 compared with baseline levels. There was a significant decrease in the bacterial gene markers (Fn, m3 and 4Bac CRC risk score) from week 2 to week 12 compared with baseline levels in the SMT04 group but not in the control group. The synbiotic formula (SMT04) is the combination of probiotic formula and several heat-resistant prebiotics. It remains unclear that whether this synbiotic formula can produce a sustained effect in reduction of advanced adenoma recurrence and colorectal neoplasia related bacterial gene markers in long-term.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects who have advanced colorectal neoplasia* removed and confirmed by histopathology;
- •They have received high quality colonoscopies before or during endoscopic resection (defined as a full colonoscopy with successful caecal intubation, and a Boston Bowel Preparation Scale ≧2 in each colonic segment) with no residual colorectal neoplasia;
- •Aged 18-90 years old;
- •Written informed consent obtained
- •An advanced colorectal neoplasia is defined as an advanced adenoma, sessile serrated lesion or non-invasive colorectal cancer (stage Tis or T1a). Advanced adenoma is defined as an adenoma larger than 10mm, and/or with villous component ≥20%, and/or harboring high grade dysplasia.
排除标准
- •Known residual colorectal neoplasia not removed (except hyperplastic polyps);
- •Contraindications to endoscopic resection due to deep submucosal invasion (stage T1b or above);
- •Prior surgical resection of colon;
- •Personal history of hereditary polyposis syndrome or inflammatory bowel disease;
- •Known pregnancy or lactation;
- •Immunocompromised status (e.g. on immunosuppressants (except 5-aminosalicylic acid or short term use of corticosteroids <4 weeks), on chemotherapy, bone marrow or solid organ transplant, human immunodeficiency virus, congenital immune deficiency);
- •Advanced comorbid conditions (defined as American Society of Anesthesiologists grade 4 or above);
- •Refusal to undergo surveillance colonoscopy.
结局指标
主要结局
The incidence of metachronous recurrent advanced colorectal neoplasia at year 1 (local or at other sites).
时间窗: 1 year
The proportion of patients with metachronous recurrent advanced neoplasia at year 1
The incidence of metachronous recurrent advanced colorectal neoplasia at year 1 (local or at other sites).
时间窗: 1 year
The proportion of patients with metachronous recurrent advanced neoplasia at year 1
次要结局
- Incidence of recurrent colorectal adenomas at year 1(1 year)
- Number of recurrent advanced neoplasia at year 1(1 year)
- Number of recurrent adenomas at year 1(1 year)
- Changes in the levels of bacterial gene markers(1 year)
- Correlation between recurrent advanced colorectal neoplasia and the changes in levels of bacterial gene markers(1 year)
- Correlation between recurrent adenoma and the changes in levels of bacterial gene markers(1 year)
- Incidence of recurrent colorectal adenomas at year 1(1 year)
- Number of recurrent advanced neoplasia at year 1(1 year)
- Number of recurrent adenomas at year 1(1 year)
- Correlation between recurrent advanced colorectal neoplasia and the changes in levels of bacterial gene markers(1 year)
- Correlation between recurrent adenoma and the changes in levels of bacterial gene markers(1 year)
研究者
Louis Ho Shing Lau
Clinical Assistant Professor
Chinese University of Hong Kong